Analyzing Neuronal and Glial Activation in Oral Tumor-Bearing Mice: Implications of Oral Cancer and Sex — 87p — Betelihiem Tecleab, Austin Walz and Jeffrey L. Barr

Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth leading cancer worldwide; it originates in the oral cavity and negatively impacts a patient’s quality of life. HNSCCs are broadly categorized into those caused by infection with high-risk human papillomavirus (HPV+) and those caused by drinking alcohol and smoking cigarettes (known as HPV-). HPV-HNSCCs account for 75% of cases, with HPV+ making up the remainder. The cancer’s location impacts functions of daily living such as eating, drinking, and speaking become compromised and cause pain. The Vermeer lab has demonstrated that HNSCCs are infiltrated with sensory nerves. Neural tracing studies have shown that these tumor-infiltrating nerves connect to a circuit that includes areas in the brain. My project will determine how oral cancer influences neuronal and glial activation in the brain. I will also assess if there are sex differences. A syngeneic model of HPV-HNSCC was implanted into the oral cavity of male and female mice. Tumor growth was monitored and brains were harvested when tumors reached euthanasia criteria. Brains from tumor-bearing and control (non-tumor) animals were sectioned using a vibratome. Brain sections were immunofluorescently stained for cFos and Fosb (markers of neuronal activity) and GFAP and Iba1 (markers of glial activation). I analyzed staining in the amygdala, parabrachial nucleus, spinal nucleus of the trigeminal, and facial nucleus as these are connected to the tumor. Stained sections were analyzed by confocal microscopy (Nikon A1 TIRF). The data collection and analysis is still ongoing. This study’s findings will increase understanding of tumor-infiltrating nerves’ impact on brain function. The tumor-to-brain connection is newly recognized; my findings will increase the understanding of how neuronal and glial functions are modulated by peripheral malignancy. If sex differences emerge, these findings may explain why male and female cancer patients experience different cognitive and emotional disturbances.

Sanford Research
Paola Vermeer